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A new approach to evaluate stability of amodiaquine and its metabolite in blood and plasma.
Dalarna University College, S-781 88 Borlänge, Sweden.
Dalarna University College, S-781 88 Borlänge, Sweden.
Dalarna University College, S-781 88 Borlänge, Sweden.
Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, UK.
2006 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 41, no 1, 207-212 p.Article in journal (Refereed) Published
Abstract [en]

A stability study for amodiaquine (AQ) and desethylamodiaquine (AQm) in whole blood and plasma is reported. AQ, AQm and chloroquine (CQ) were simultaneously analysed and the ratios AQ/CQ and AQm/CQ were used to ensure correct interpretation of the stability results. CQ was stable in whole blood and plasma at all tested temperatures enabling it to be a stability marker in stability studies. Simultaneous analysis of compounds, of which at least one is already known to be stable, permits a within sample ratio to be used as a stability indicator. The new approach significantly reduced bias when compared to the traditional approach. AQ and AQm were stable in plasma at -86 degrees C and -20 degrees C for 35 days, at 4 degrees C for 14 days and at 22 degrees C for 1 day. AQ and AQm were stable in blood at -86 degrees C and 4 degrees C for 35 days, at -20 degrees C and 22 degrees C for 7 days and at 37 degrees C for 1 day.

Place, publisher, year, edition, pages
2006. Vol. 41, no 1, 207-212 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-108744DOI: 10.1016/j.jpba.2005.10.018ISI: 000236655100028PubMedID: 16307860OAI: oai:DiVA.org:uu-108744DiVA: diva2:240690
Available from: 2009-09-29 Created: 2009-09-29 Last updated: 2013-06-20Bibliographically approved
In thesis
1. Development of Analytical Methods for the Determination of Antimalarials in Biological Fluids
Open this publication in new window or tab >>Development of Analytical Methods for the Determination of Antimalarials in Biological Fluids
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to develop analytical methods for measuring antimalarial drugs in biological fluids. Solid phase extraction (SPE) was used for the enrichment and purification of the drugs. Automatic extraction procedures using a SPE robot were developed to reduce the workload for the analyst and to minimize variations in the extraction procedure. Liquid chromatography (LC) with either UV or mass spectrometric (MS) detection was used to determine sample concentrations.

Determination of Pyronaridine in whole blood utilised a weak cation exchanger to extract Pyronaridine from blood. To improve LC separation between Pyronaridine and the internal standard, ion-pairing was utilized.

For the simultaneous quantification of the highly lipophilic Atovaquone and the strong basic drug Proguanil with metabolites, a novel mixed mode solid phase extraction column was used. It combines the properties of a carboxylic acid (CBA) column and a non-polar octyl-silica (C8) column to extract the compounds from plasma; it also required a gradient LC separation.

Stability is an important factor when developing new methods. A new approach was used to evaluate the stability of Amodiaquine in blood and plasma. This included the use of a stability marker, a stable compound which was added together with Amodiaquine when preparing the stability samples. This eliminated between-run variations and variations associated with preparation of new stock solutions.

Lumefantrine (LF) is one of the active components in a new drug combination recommended by the World Health Organization as a replacement for older drugs which have lost their effect. The first of the two methods described for this compound is the determination of LF and a possible metabolite in plasma with a calibration range suitable for pharmacokinetic studies. In the second method, a capillary sampling technique is used where the blood is dried on a sampling paper and sent to the laboratory where the extraction and determination of LF concentrations take place. This method facilitates sample collection and will enable drug efficacy studies conducted in rural settings.

To monitor a current change in treatment policy and self medication, a screening assay was developed. Its purpose is to be a complement to interviewing patients about their previous medication (in the previous few weeks) and to detect some of the more common drugs which might have been used.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 52 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 676
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-108767 (URN)978-91-554-7620-5 (ISBN)
Public defence
2009-11-12, Clas Ohlson room, Humanistgatan 2, Tenoren, Högskolan Dalarna, Borlänge, 13:00 (Swedish)
Opponent
Supervisors
Note
Paper 6. as ManuscriptAvailable from: 2009-10-22 Created: 2009-09-29 Last updated: 2009-10-22Bibliographically approved

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